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1.
Poult Sci ; 103(10): 104107, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39094499

ABSTRACT

Plumage color is an intuitive external poultry characteristic with rich manifestations and complex genetic mechanisms. In our previous study, we observed that there were more dark variations in plumage color in the F2 population derived from the hybridization of 2 white duck varieties. Therefore, based on the statistics of plumage color of 308 F2 populations, we further used the resequencing data of these individuals to detect copy number variations (CNVs) in the whole genome and conducted genome-wide association studies (GWAS) to determine the genetic basis related to plumage color traits. The CNV detection revealed 9,337 CNVs, with an average length of 15,950 bp and a total length of 142.02 MB, accounting for approximately 12.91% of the reference genome. The CNV distribution on the chromosomes was relatively uniform, and the number of CNVs on each chromosome positively correlated with the length of the chromosome. In the pure black plumage group, 2,101 CNVs were only identified, and 1,714 were specifically identified in the pure white plumage group. Ten CNVs were randomly selected for validation using quantitative real-time PCR, and 9 CNVs had the same CNV types as predicted, with an accuracy of 90%. Based on GWAS, we identified 2 CNVs potentially associated with plumage color variations, with the associated CNV regions covering 9 genes. Enrichment analysis of these 9 candidate genes showed significant enrichment of 3 pathways (ribosome biogenesis in eukaryotes, RNA transport, and protein export) and 17 gene ontology terms. Among these, VWA5A can downregulate MITF by binding to the regulatory factors SOX10. The occurrence of CNV may indirectly contribute to duck plumage color variation by affecting the regulatory factors of the switch gene MITF in the melanogenesis pathway. These findings have improved the understanding of the genetic basis of duck plumage color variation and have been beneficial for developing and using plumage color traits in subsequent poultry breeding.

2.
ACS Macro Lett ; : 1099-1104, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39132974

ABSTRACT

Chemical recycling of polymers to the corresponding monomers offers a valuable solution to address the current plastics crisis for creating an ideal and circular polymer economy. Here, we present a bimetallic synergistic depolymerization of the widely studied CO2-based polycarbonates, poly(cyclohexene carbonate)s, to epoxide monomers efficiently. The bimetallic CrIII-complex-mediated highly selective depolymerization and repolymerization was achieved via the regulation of reaction temperature, thus closing the circular loop of poly(cyclohexene carbonate)s in situ. Mechanistic investigation has revealed that the formation of epoxides undergoes a direct chain-end unzipping process. A bimetallic catalysis involving a nucleophilic attack of the metal-alkoxide species toward the methine carbon atom bound with an adjacent carbonyl that is activated by the other metal center features a lower energy barrier in DFT calculations, which promotes the epoxide extrusion.

3.
Talanta ; 279: 126660, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39116733

ABSTRACT

Detecting the furfural concentration in Baijiu can be used to assess the quality of Baijiu, allowing for the optimization of processing techniques and the enhancement of overall quality. In this paper, a fluorescence-enhanced method based on carbon dots (o-CDs) is developed for the furfural determination in Chinese Baijiu. In an environment full-filled with ·SO4- and ·OH, furfural undergone a direct surface reaction with the ortho-diamino groups at o-CDs. The created furan-based imidazole increased the surface electron density, leading an emission enhancement and color changes from orange to green. Thereby, a linear fluorescence response of o-CDs-TA to furfural is established in water with a detection limit of 30.5 nM. Finally, after ethanol correction it is used to determine furfural in Chinese Baijiu with high precision and reproducibility, providing a new strategy with low-cost and high sensitivity. In particular, the idea of covalently connecting target molecule to the CDs surface via the assistance of free radical opens a new avenue to merge the nanoscale and molecular realms through implementing chemical role into carbon nanostructures.

4.
Animals (Basel) ; 14(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39123780

ABSTRACT

To meet the demand of consumers for chicken products, poultry breeders have made improvements to chickens. However, this has led to a new problem in the modern poultry industry, namely excessive fat deposition. This study aims to understand the effects of dietary iron supplementation on fat deposition and gut microbiota in chickens. In this study, we investigated the effects of iron on the growth performance, fat deposition, and gut microbiota of silky fowl black-bone chickens. A total of 75 7-week-old silky fowl black-bone chickens were randomly divided into three groups (five replicates per group, five chickens per replicate) and fed them for 28 days using a growing diet (control group), a growing diet + 10% tallow (high-fat diet group, HFD group), and a growing diet + 10% tallow + 500 mg/kg iron (HFDFe500 group), respectively. We detected the effects of iron on the growth performance, fat deposition, and gut microbiota of silky fowl black-bone chickens using the growth performance index test, oil red O staining, and HE staining, and found that the high-fat diet significantly increased liver and serum fat deposition and liver injury, while the addition of iron to the diet could reduce the fat deposition caused by the high-fat diet and alleviate liver injury. In addition, 16S rDNA sequencing was used to compare the relative abundance of gut microbiota in the cecal contents in different feeding groups. The results showed that the high-fat diet could induce gut microbiota imbalance in chickens, while the high-iron diet reversed the gut microbiota imbalance. PICRUSt functional prediction analysis showed that dietary iron supplementation affected amino acid metabolism, energy metabolism, cofactors, and vitamin metabolism pathways. In addition, correlation analysis showed that TG was significantly associated with Firmicutes and Actinobacteriota (p < 0.05). Overall, these results revealed high dietary iron (500 mg/kg) could reduce fat deposition and affect the gut microbiota of silky fowl black-bone chickens, suggesting that iron may regulate fat deposition by influencing the gut microbiota of chickens and provides a potential avenue that prevents excessive fat deposition in chickens by adding iron to the diet.

5.
Int J Mol Sci ; 25(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39125712

ABSTRACT

Liver lipid metabolism disruption significantly contributes to excessive fat buildup in waterfowl. Research suggests that the supplementation of Threonine (Thr) in the diet can improve liver lipid metabolism disorder, while Thr deficiency can lead to such metabolic disorders in the liver. The mechanisms through which Thr regulates lipid metabolism remain unclear. STAT3 (signal transducer and activator of transcription 3), a crucial transcription factor in the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway, participates in various biological processes, including lipid and energy metabolism. This research investigates the potential involvement of STAT3 in the increased lipid storage seen in primary duck hepatocytes as a result of a lack of Thr. Using small interfering RNA and Stattic, a specific STAT3 phosphorylation inhibitor, we explored the impact of STAT3 expression patterns on Thr-regulated lipid synthesis metabolism in hepatocytes. Through transcriptome sequencing, we uncovered pathways related to lipid synthesis and metabolism jointly regulated by Thr and STAT3. The results showed that Thr deficiency increases lipid deposition in primary duck hepatocytes (p < 0.01). The decrease in protein and phosphorylation levels of STAT3 directly caused this deposition (p < 0.01). Transcriptomic analysis revealed that Thr deficiency and STAT3 knockdown jointly altered the mRNA expression levels of pathways related to long-chain fatty acid synthesis and energy metabolism (p < 0.05). Thr deficiency, through mediating STAT3 inactivation, upregulated ELOVL7, PPARG, MMP1, MMP13, and TIMP4 mRNA levels, and downregulated PTGS2 mRNA levels (p < 0.01). In summary, these results suggest that Thr deficiency promotes lipid synthesis, reduces lipid breakdown, and leads to lipid metabolism disorders and triglyceride deposition by downregulating STAT3 activity in primary duck hepatocytes.


Subject(s)
Ducks , Hepatocytes , STAT3 Transcription Factor , Threonine , Triglycerides , Animals , STAT3 Transcription Factor/metabolism , Hepatocytes/metabolism , Phosphorylation , Threonine/metabolism , Triglycerides/metabolism , Lipid Metabolism , Cells, Cultured
6.
Poult Sci ; 103(10): 104139, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39127007

ABSTRACT

The wide distribution and diverse varieties of chickens make them important models for studying genetic adaptation. The aim of this study was to identify genes that alter heat adaptation in commercial chicken breeds by comparing genetic differences between tropical and cold-resistant chickens. We analyzed whole-genome resequencing data of 186 chickens across various regions in Asia, including the following breeds: Bian chickens (B), Dagu chickens (DG), Beijing-You chickens (BY), and Gallus gallus jabouillei from China; Gallus gallus murghi from India; Vietnam native chickens (VN); Thailand native chickens (TN) and Gallus gallus spadiceus from Thailand; and Indonesia native chickens (IN), Gallus gallus gallus, and Gallus gallus bankiva from Indonesia. In total, 5,454,765 SNPs were identified for further analyses. Population genetic structure analysis revealed that each local chicken breed had undergone independent evolution. Additionally, when K = 5, B, BY, and DG chickens shared a common ancestor and exhibited high levels of inbreeding, suggesting that northern cold-resistant chickens are likely the result of artificial selection. In contrast, the runs of homozygosity (ROH) and the ROH-based genomic inbreeding coefficient (FROH) results for IN, TN, and VN chickens showed low levels of inbreeding. Low population differentiation index values indicated low differentiation levels, suggesting low genetic diversity in tropical chickens, implying increased vulnerability to environmental changes, decreased adaptability, and disease resistance. Whole-genome selection sweep analysis revealed 69 candidate genes, including LGR4, G6PC, and NBR1, between tropical and cold-resistant chickens. The genes were further subjected to GO and KEGG enrichment analyses, revealing that most of the genes were primarily enriched in biological synthesis processes, metabolic processes, central nervous system development, ion transmembrane transport, and the Wnt signaling pathway. Our study identified heat adaptation genes and their functions in chickens that primarily affect chickens in high-temperature environments through metabolic pathways. These heat-resistance genes provide a theoretical basis for improving the heat-adaptation capacity of commercial chicken breeds.

7.
J Mater Chem B ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082127

ABSTRACT

The ion-sensitive field effect transistor (ISFET) has emerged as a crucial sensor device, owing to its numerous benefits such as label-free operation, miniaturization, high sensitivity, and rapid response time. Currently, ISFET technology excels in detecting ions, nucleic acids, proteins, and cellular components, with widespread applications in early disease screening, condition monitoring, and drug analysis. Recent advancements in sensing techniques, coupled with breakthroughs in nanomaterials and microelectronics, have significantly improved sensor performance. These developments are steering ISFETs toward a promising future characterized by enhanced sensitivity, seamless integration, and multifaceted detection capabilities. This review explores the structure and operational principles of ISFETs, highlighting recent research in ISFET biosensors for biomarker detection. It also examines the limitations of these sensors, proposes potential solutions, and anticipates their future trajectory. This review aims to provide a valuable reference for advancing ISFETs in the field of biomarker measurement.

8.
Nat Commun ; 15(1): 5975, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013854

ABSTRACT

Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables-ferroelectric polarization and magnetization-we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

9.
ACS Appl Mater Interfaces ; 16(31): 41202-41210, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39056202

ABSTRACT

Lightweight and strong ceramic materials are attractive for tissue engineering, aerospace, armor systems, and many high-temperature applications. Cuttlebone, primarily composed of bioceramics, features a unique S-shaped wall structure that contributes significantly to its remarkable mechanical properties. Here, we explore the hierarchical structure and components of the cuttlebone and reveal the high ceramic content in S-shaped walls. Inspired by the design of the cuttlebone, we developed a high ceramic loading slurry for three-dimensional printing cuttlebone-like structures. As shown in the compression test, the fabricated bioinspired ceramics exhibit excellent mechanical properties and can withstand 1.07 million times their own weight, outperforming traditional ceramic foams. The specific strength and modulus are 59.5 and 785.6 MPa/(g cm-3), 9 and 36 times that of the natural cuttlebone. The failure mechanisms are also systematically studied on the basis of tuning the structural parameters. These findings provide effective solutions and inspiration in fabricating high-performance ceramic structural materials.

10.
Int J Biol Macromol ; 275(Pt 1): 133644, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38964687

ABSTRACT

Apoptosis plays a crucial role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J), an avian oncogenic retrovirus, has been shown to suppress apoptosis while promoting its own replication. ALV-J induces myeloid tumors and hemangiomas in chickens resulting in significant economic losses for commercial layer and meat-type chicken production. B-cell lymphoma/leukemia 11B (Bcl11b) encodes a C2H2-type zinc finger protein-BCL11B, that exerts critical functions in cell proliferation, differentiation, and plays an essential role in the immune system. Previous study has been shown that Bcl11b is associated with ALV-J infection. In this study, we further investigated the pathological changes in ALV-J infected cells and examined the role and expression regulation of chicken Bcl11b. Our results demonstrate that Bcl11b, as an interferon-stimulated gene (ISG), encodes C2H2-type zinc finger protein BCL11B that promotes apoptosis to inhibit ALV-J infection. Additionally, gga-miR-1612 and gga-miR-6701-3p regulate apoptosis and are involved in ALV-J infection by targeting Bcl11b, thus revealing immune response strategies between the host and ALV-J. Although the underlying mechanisms require further validation, Bcl11b and its regulatory miRNAs are the first to demonstrate inhibition of ALV-J replication via apoptosis. BCL11B can a valuable target for treating diseases triggered by ALV-J infection.


Subject(s)
Apoptosis , Avian Leukosis Virus , Avian Leukosis , Chickens , Virus Replication , Avian Leukosis Virus/physiology , Animals , Avian Leukosis/virology , MicroRNAs/genetics , MicroRNAs/metabolism , Zinc Fingers , Repressor Proteins/genetics , Repressor Proteins/metabolism , Gene Expression Regulation
11.
Front Microbiol ; 15: 1377763, 2024.
Article in English | MEDLINE | ID: mdl-38962139

ABSTRACT

Introduction: Arbuscular mycorrhizal fungi (AMF) are vital in terrestrial ecosystems. However, the community structure characteristics and influencing factors of AMF in the forest ecosystems of arid desert grassland areas require further investigation. Methods: Therefore, we employed high-throughput sequencing technology to analyze the soil AMF community characteristics at different elevations in the Helan mountains. Results: The results revealed that significant differences (P < 0.05) were observed in the soil physicochemical properties among different elevations, and these properties exhibited distinct trends with increasing elevation. Through high-throughput sequencing, we identified 986 operational taxonomic units (OTUs) belonging to 1 phylum, 4 classes, 6 orders, 12 families, 14 genera, and 114 species. The dominant genus was Glomus. Furthermore, significant differences (P < 0.05) were observed in the α-diversity of the soil AMF community across different elevations. Person correlation analysis, redundancy analysis (RDA), and Monte Carlo tests demonstrated significant correlations between the diversity and abundance of AMF communities with soil organic matter (OM) (P < 0.01) and soil water content (WC) (P < 0.05). Discussion: This study provides insights into the structural characteristics of soil AMF communities at various altitudes on the eastern slope of Helan mountain and their relationships with soil physicochemical properties. The findings contribute to our understanding of the distribution pattern of soil AMF and its associations with environmental factors in the Helan mountains, as well as the stability of forest ecosystems in arid desert grassland areas.

12.
BMC Cancer ; 24(1): 715, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862908

ABSTRACT

BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. METHODS: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. RESULTS: Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. CONCLUSION: Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. TRIAL REGISTRATION: NCT04507906 August 11, 2020.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Nivolumab , Protein Kinase Inhibitors , Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Drug Resistance, Neoplasm , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Indoles/administration & dosage , Indoles/adverse effects , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Nivolumab/administration & dosage , Nivolumab/adverse effects , Nivolumab/therapeutic use , Prospective Studies , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Quinolines/administration & dosage , Quinolines/adverse effects , Quinolines/therapeutic use , Adolescent
13.
Genome Med ; 16(1): 81, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38872215

ABSTRACT

BACKGROUND: Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. METHODS: To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. RESULTS: Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose-response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). CONCLUSIONS: Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Female , Male , Middle Aged , Aged , Risk Assessment , Polymorphism, Single Nucleotide , Bayes Theorem , Risk Factors
14.
Bioact Mater ; 39: 287-301, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38827170

ABSTRACT

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

15.
Cell Death Differ ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902548

ABSTRACT

Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a m6A methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects. Subsequently, we identified TRIP12, a HECT-domain E3 ubiquitin ligase, as a negative regulator of METTL3 protein expression by facilitating METTL3 K48-linked polyubiquitination. Importantly, selective ablation of Mettl3 inhibited microglial pathogenic activities, diminished neutrophil infiltration, rescued neuronal loss and facilitated functional recovery post-TBI. Using MeRIP-seq and CUT&Tag sequencing, we identified that METTL3 promoted the expression of Basic Leucine Zipper Transcriptional Factor ATF-Like (BATF), which in turn directly bound to a cohort of characteristic inflammatory cytokines and chemokine genes. Enhanced activities of BATF in microglia elicited TNF-dependent neurotoxicity and can also promote neutrophil recruitment through releasing CXCL2. Pharmacological inhibition of METTL3 using a BBB-penetrating drug-loaded nano-system showed satisfactory therapeutic effects in both TBI and stroke mouse models. Collectively, our findings identified METTL3-m6A-BATF axis as a potential therapeutic target for terminating detrimental neuroinflammation and progressive neuronal loss following acute brain injury. METTL3 protein is significantly up-regulated in inflammatory microglia due to the decreased proteasomal degradation mediated by TRIP12 and ERK-USP5 pathways. METTL3 stabilized BATF mRNA stability and promoted BATF expression through the m6A-IGF2BP2-dependent mechanism. Elevated expression of BATF elicits a pro-inflammatory gene program in microglia, and aggravates neuroinflammatory response including local immune responses and peripheral immune cell infiltration. Genetic deletion or pharmaceutically targeting METTL3-BATF axis suppressed microglial pro-inflammatory activities and promoted neurological recovery following TBI and stroke.

16.
Sensors (Basel) ; 24(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38894454

ABSTRACT

The high-speed railway subgrade compaction quality is controlled by the compaction degree (K), with the maximum dry density (ρdmax) serving as a crucial indicator for its calculation. The current mechanisms and methods for determining the ρdmax still suffer from uncertainties, inefficiencies, and lack of intelligence. These deficiencies can lead to insufficient assessments for the high-speed railway subgrade compaction quality, further impacting the operational safety of high-speed railways. In this paper, a novel method for full-section assessment of high-speed railway subgrade compaction quality based on ML-interval prediction theory is proposed. Firstly, based on indoor vibration compaction tests, a method for determining the ρdmax based on the dynamic stiffness Krb turning point is proposed. Secondly, the Pso-OptimalML-Adaboost (POA) model for predicting ρdmax is determined based on three typical machine learning (ML) algorithms, which are back propagation neural network (BPNN), support vector regression (SVR), and random forest (RF). Thirdly, the interval prediction theory is introduced to quantify the uncertainty in ρdmax prediction. Finally, based on the Bootstrap-POA-ANN interval prediction model and spatial interpolation algorithms, the interval distribution of ρdmax across the full-section can be determined, and a model for full-section assessment of compaction quality is developed based on the compaction standard (95%). Moreover, the proposed method is applied to determine the optimal compaction thicknesses (H0), within the station subgrade test section in the southwest region. The results indicate that: (1) The PSO-BPNN-AdaBoost model performs better in the accuracy and error metrics, which is selected as the POA model for predicting ρdmax. (2) The Bootstrap-POA-ANN interval prediction model for ρdmax can construct clear and reliable prediction intervals. (3) The model for full-section assessment of compaction quality can provide the full-section distribution interval for K. Comparing the H0 of 50~60 cm and 60~70 cm, the compaction quality is better with the H0 of 40~50 cm. The research findings can provide effective techniques for assessing the compaction quality of high-speed railway subgrades.

17.
Animals (Basel) ; 14(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891603

ABSTRACT

The demand for high-quality chilled chicken has continued to increase in China. Chickens are sexually dimorphic, and to better understand the specific differences in chicken production based on sex, we examined how sex affects growth performance, carcass traits, and meat quality of yellow-feathered chickens. Male and female Xueshan chickens were used as the experimental model. Although males exhibited better growth performance, including body weight (BW), body slope, keel, shank length, and shank girth (p < 0.05), as well as carcass traits, such as dressed weight, leg muscle, and lean meat, females had higher carcass and breast muscle yields (p < 0.05). Males had higher follicle density and yellowness (b*) of the skin and better skin than females (p < 0.05). Among blood biochemical parameters, the serum content of corticosterone (CORT) was higher in males, while those of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), and catalase (CAT) were lower in males than in females (p < 0.05). The pH levels, shear force, and moisture content quality were better in male breast meat, while the intramuscular fat content (IMF) was lower in males than in females (p < 0.05). The redness (a*) and moisture content were higher in male leg meat, while the pH, water-loss rate (WLR), lightness (L*), and IMF were lower (p < 0.05). The muscle fiber diameter and cross-sectional area were also higher in males (p < 0.05). Consumers felt that soup of male chicken was better than female (p < 0.05), while mouthfeel and tenderness acceptance of breast meat were different between the sexes. These results indicate that female chickens can be marketed as a whole carcass, while males are more suitable for processed carcass products. This study provides significant insights into the production and processing methodologies of yellow-feathered chickens.

18.
Poult Sci ; 103(7): 103778, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703760

ABSTRACT

The gut-brain axis is essential in maintaining the homeostasis of neuronal system, endocrine system, and intestinal microbiota in both the afferent and efferent directions. This axis is considered to be a key mechanism that regulates feed efficiency (FE). This study aimed to investigate the regulatory mechanisms of gut-brain axis-related genes on the residual feed intake (RFI) in H-strain small-sized meat ducks. A total of 500 ducks with similar initial BW (635.2 ± 15.1 g) were selected and reared in the same experimental facility until slaughter at 42 d of age. RFI was calculated from the average daily gain (ADG), average daily feed intake (ADFI), and metabolic body weight (MBW0.75). Thirty high-RFI (H-RFI) and 30 low-RFI (L-RFI) birds were selected for further evaluation of growth performance, carcass characteristics, and blood biochemical parameter measurements. Six L-RFI and 6 H-RFI birds were then subjected to hypothalamic transcriptomic and cecal microbial sequencing analyses. Results indicated that L-RFI birds exhibited lower production performance (ADFI, FCR, and RFI) and blood biochemical indices (total cholesterol and ghrelin content) compared with H-RFI birds (P < 0.05). Gene expression differed significantly between the L-RFI and H-RFI birds, with 70 upregulated and 50 downregulated genes. The bacterial communities of L-RFI birds showed higher abundances of Bacteroides, Bifidobacterium, and Lactococcus, and lower abundances of Erysipelatoclostridium, Parasutterella, Fournierella, and Blautia compared with H-RFI birds (P < 0.05). Interactive analysis revealed bacterial communities associated with FE were significantly correlated with hypothalamic genes (P < 0.05), for example, Bacteroides was positively correlated with DGKH and LIPT2, while negatively correlated with CAPN9, GABRD, and PDE1A. Bifidobacterium showed significant correlations with ATP2A3, CALHM6, and TMEM121B. Overall, RFI was a crucial indicator of FE, regulated by interactions between brain gene expression and gut microbiota through cAMP signaling, neuroactive ligand-receptor interaction, and calcium signaling pathways. Notably, increased expression of hypothalamic genes and abundance of carbohydrate-utilization microbiota in L-RFI meat ducks improved FE by enhancing energy metabolism and volatile fatty acids absorption.


Subject(s)
Ducks , Gastrointestinal Microbiome , Animals , Ducks/physiology , Ducks/growth & development , Ducks/genetics , Gastrointestinal Microbiome/physiology , Brain-Gut Axis/physiology , Eating , Male
19.
Poult Sci ; 103(7): 103836, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38776859

ABSTRACT

In this study, we sought to determine the effects of intestinal flora on the feed efficiency of meat ducks by evaluating the correlation between intestinal flora and residual feed intake. The F2 generation of Cherry Valley ducks × Runzhou Crested White ducks was used as the study subjects, and feed consumption being recorded from d 21 to 42. RFI was calculated based on growth performance, and 20 low RFI and 20 high RFI ducks were randomly selected to characterize the effect of RFI on growth performance. To analyze the intestinal flora affecting RFI, 16s rDNA sequencing was performed on the contents of 5 intestinal segments from the HR and LR groups, and macrogenomic sequencing was performed on the cecal contents. Feed intake, average daily feed intake, feed conversion ratio, and residual feed intake were lower in low RFI. Analysis of the intestinal flora revealed the cecum to be more highly enriched in the carbohydrate metabolism pathway and less enriched with potentially pathogenic taxa than the other assessed intestinal regions. Further analysis of the cecal microbiota identified nine significantly differentially enriched intestinal flora. In this study, we accordingly identified a basis for the mechanisms underlying the effects of the intestinal flora on meat duck feed efficiency.


Subject(s)
Ducks , Gastrointestinal Microbiome , Animals , Ducks/microbiology , RNA, Ribosomal, 16S/analysis , Animal Feed/analysis , Male , Cecum/microbiology , Eating , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
20.
Front Nutr ; 11: 1373709, 2024.
Article in English | MEDLINE | ID: mdl-38751744

ABSTRACT

Objective: The oxidative balance score (OBS) is important for determining the cause of obesity and its complications. We aimed to evaluate the association between OBS and obesity and other segmental body composition parameters among young and middle-aged U.S. adults. Methods: 9,998 participants from the National Health and Nutrition Examination Survey 2011-2018 were included. Lean mass percentage (LM%) and FM% were evaluated by dual-energy x-ray absorptiometry. Obesity was defined as body FM% ≥25% in men and ≥ 35% in women. The OBS was scored by 5 pro-oxidant and 21 antioxidant factors. Associations of quartiles of OBS with obesity risk were estimated using multivariable logistic regression models. Multivariable linear regression was conducted to estimate the association between OBS and segmental body composition measures including the arm LM%, leg LM%, torso LM%, whole LM%, arm FM%, leg FM%, torso FM% and total FM%. Results: Compared to participants in the lowest quartile of OBS, those in the highest quartile of OBS were associated with a lower risk of BMI-defined obesity BMI-defined obesity [0.43 (0.36, 0.50)] and FM%-related obesity [0.43 (0.35, 0.52)]. Additionally, OBS was negatively associated with FM% of the limb and torso but positively associated with the percentage of lean mass (LM%) of the limb and trunk. Conclusion: OBS was negatively associated with the risk of obesity and segmental FM%, but was positively associated with segmental LM% among US adults, indicating that adhering to an anti-oxidative diet and lifestyle management may be beneficial for preventing segmental obesity.

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